The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F16%3A33161527" target="_blank" >RIV/61989592:15310/16:33161527 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/16:33161527

Výsledek na webu

<a href="http://dmd.aspetjournals.org/content/44/4/576" target="_blank" >http://dmd.aspetjournals.org/content/44/4/576</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1124/dmd.115.068569" target="_blank" >10.1124/dmd.115.068569</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function

Popis výsledku v původním jazyce

This symposium summary, sponsored by the ASPET, was held at Experimental Biology 2015 on March 29, 2015, in Boston, Massachusetts. The symposium focused on: 1) the interactions of cytochrome P450s (P450s) with their redox partners; and 2) the role of the lipid membrane in their orientation and stabilization. Two presentations discussed the interactions of P450s with NADPH-P450 reductase (CPR) and cytochrome b(5). First, solution nuclear magnetic resonance was used to compare the protein interactions that facilitated either the hydroxylase or lyase activities of CYP17A1. The lyase interaction was stimulated by the presence of b(5) and 17 alpha-hydroxypregnenolone, whereas the hydroxylase reaction was predominant in the absence of b(5). The role of b(5) was also shown in vivo by selective hepatic knockout of b(5) from mice expressing CYP3A4 and CYP2D6; the lack of b(5) caused a decrease in the clearance of several substrates. The role of the membrane on P450 orientation was examined using computational methods, showing that the proximal region of the P450 molecule faced the aqueous phase. The distal region, containing the substrate-access channel, was associated with the membrane. The interaction of NADPH-P450 reductase (CPR) with the membrane was also described, showing the ability of CPR to "helicopter" above the membrane. Finally, the endoplasmic reticulum (ER) was shown to be heterogeneous, having ordered membrane regions containing cholesterol and more disordered regions. Interestingly, two closely related P450s, CYP1A1 and CYP1A2, resided in different regions of the ER. The structural characteristics of their localization were examined. These studies emphasize the importance of P450 protein organization to their function.

Název v anglickém jazyce

The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function

Popis výsledku anglicky

This symposium summary, sponsored by the ASPET, was held at Experimental Biology 2015 on March 29, 2015, in Boston, Massachusetts. The symposium focused on: 1) the interactions of cytochrome P450s (P450s) with their redox partners; and 2) the role of the lipid membrane in their orientation and stabilization. Two presentations discussed the interactions of P450s with NADPH-P450 reductase (CPR) and cytochrome b(5). First, solution nuclear magnetic resonance was used to compare the protein interactions that facilitated either the hydroxylase or lyase activities of CYP17A1. The lyase interaction was stimulated by the presence of b(5) and 17 alpha-hydroxypregnenolone, whereas the hydroxylase reaction was predominant in the absence of b(5). The role of b(5) was also shown in vivo by selective hepatic knockout of b(5) from mice expressing CYP3A4 and CYP2D6; the lack of b(5) caused a decrease in the clearance of several substrates. The role of the membrane on P450 orientation was examined using computational methods, showing that the proximal region of the P450 molecule faced the aqueous phase. The distal region, containing the substrate-access channel, was associated with the membrane. The interaction of NADPH-P450 reductase (CPR) with the membrane was also described, showing the ability of CPR to "helicopter" above the membrane. Finally, the endoplasmic reticulum (ER) was shown to be heterogeneous, having ordered membrane regions containing cholesterol and more disordered regions. Interestingly, two closely related P450s, CYP1A1 and CYP1A2, resided in different regions of the ER. The structural characteristics of their localization were examined. These studies emphasize the importance of P450 protein organization to their function.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Drug Metabolism and Disposition

ISSN

0090-9556

e-ISSN

—

Svazek periodika

44

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

576-590

Kód UT WoS článku

000372880600014

EID výsledku v databázi Scopus

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